This program project will continue research in the use of heavy charged particles such as helium and neon ions for treatment of human cancers. The physical parameters of protons and helium ions permit precision charged particle radiation therapy to be delivered, resulting in highly significant clinical advances in the treatment of tumors lying close to critical normal structures in the eye, orbit, skull base, paranasal sinuses, juxtaspinal area, retroperitoneum or pelvis. Optimization of the use of these low-LET charged particles will continue, as LBL beam availability permits, through collaboration with other proton facilities in cooperative clinical trials. Neon ions, in addition to their dose-localizing properties, offer greater biological effectiveness because of their high-LET. Clinical promise has been seen in neon ion preliminary trials in bone and soft tissue sarcoma, prostate cancer, salivary gland tumors, skull base tumors such as nasopharynx and paranasal sinus cancers, juxtaspinal tumors and biliary tract tumors. Prospective trials are underway to determine whether dose- localization alone (Protons or Helium ions) is comparable to dose- localization + high-LET (Neon ions) therapy. Neon ions are also being compared to megavoltage low-LET therapy in treatment of prostate tumors and glioblastoma of the brain. It is expected that added clinical gains will be achieved through further research and development of improved treatment delivery techniques, specifically implementation of dynamic conformal heavy charged particle therapy. Potentially, highly significant improvement in high-LET charged particle therapy will be possible through much improved conformation f the high-LET dose zone to the tumor, with sparing of normal tissues both proximal and distal to the tumor. Improvements in treatment planning will be made to implement this highly promising form of charged particle therapy. The goals of the program are to optimize low-LET dose-localization therapy with protons and helium ions, and to study the application of high-LET beams such as neon ions in the treatment of human cancers.